LAUSR

Abstract Background The VNR/Cis chemotherapy doublet has been evaluated in prior positive adjuvant trials in patients with completely resected Ns-NSCLC, whereas no phase III study has so far evaluated PEM/Cis in this population. And there are few data regarding outcomes based on EGFR mutation (EGFRm) status in adjuvant chemotherapies. Methods Patients with completely resected Ns-NSCLC were randomized in a 1:1 ratio to receive either PEM (500 mg/m2, day 1)/Cis (75 mg/m2, day 1) or VNR (25 mg/m2, days 1 and 8)/Cis (80 mg/m2, day 1), and stratified according to sex, age, pathologic stage, EGFRm status and institution. The primary endpoint was recurrence-free survival (RFS), and, the planned sample size was 800 patients in total (Trial Identifier, UMIN000006737). Results Between March 2012 and August 2016, 804 patients were randomized. Of 784 for the efficacy analysis (389 in PEM/Cis and 395 in VNR/Cis), median age was 65/65 years; stage IIIA 52.2%/52.4%; adenocarcinoma, 95.9%/95.9%; and EGFR mutation, 24.1%/24.9%. With a median follow-up of 45.2 months (mo), median RFS was 38.9mo in PEM/Cis and 37.3mo in VNR/Cis with a hazard ratio (HR) of 0.98 (95% CI, 0.81--1.20; log-rank test, P = 0.948), whereas HRs in patients with or without EGFRm were 1.38 (95% CI, 0.95--1.99) and 0.87 (95% CI, 0.69--1.09), respectively (Interaction, P = 0.046). As for patients without EGFRm, median RFS was 65.2mo in PEM/Cis and 39.9mo in VNR/Cis. The overall survival rate at 3 years was 83.5% versus 87.2% with a HR of 0.98 (95% CI, 0.71 --1.35). Rates of treatment completion were 87.9% (PEM/Cis) and 72.7% (VNR/Cis), respectively (P  Conclusions Although this phase III study did not meet the primary endpoint, PEM/CDDP had a similar efficacy to VNR/CDDP with a better tolerability as postoperative adjuvant chemotherapy for Ns-NSCLC patients. A significant interaction for RFS was found between treatment and EGFR mutation status. In patients without EGFR mutation, PEM/Cis seems to be a preferable regimen as the adjuvant chemotherapy. Clinical trial identification UMIN000006737. Legal entity responsible for the study The authors. Funding Health and Labor Sciences Research Grants, The Japan Agency of Medical Research and Development (AMED). Disclosure M. Tsuboi: Honoraria (self): AstraZeneca KK; Honoraria (self): Johnson & Johnson Japan; Honoraria (self): MSD; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharma; Honoraria (self): Eli Lilly Japan; Honoraria (self): Boehringer Ingelheim Japan; Honoraria (self): Ono Pharmaceutical Co., Ltd; Honoraria (self): Bristol-Myers Squibb KK; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Covidien Japan; Honoraria (self): Teijin Pharma; Research grant / Funding (institution): Boehringer Ingelheim Japan. All other authors have declared no conflicts of interest.